Human gut organoids a next-generation platform for translational research

At the Centre for Children’s Gut Health, we harness the power of patient-derived intestinal organoids (IEOs) to investigate the cellular and molecular underpinnings of paediatric gastrointestinal disease — with a clear focus on clinical translation.

Derived from minimally invasive endoscopic biopsies, IEOs are three-dimensional, self-renewing cultures that recapitulate key features of the human intestinal epithelium, including gut segment identity, stem cell function, and barrier properties. Unlike traditional 2D cell lines, these models retain epigenetic, transcriptional, and functional signatures of the patient’s original tissue, enabling physiologically relevant research in vitro.

Our group has established one of the world’s largest paediatric IBD organoid biobanks, now serving as a cornerstone of the ORBIT-IBD global research programme. These models enable us to:

• Investigate disease mechanisms, using CRISPR-based gene editing, single-cell and spatial transcriptomics, and epithelial–immune co-culture systems.
• Validate clinically relevant biomarkers, such as DNA methylation patterns that are stable in vitro and correlate with disease activity and treatment response (Dennison et al., Gut, 2024).
• Model therapeutic responses, simulating the effect of biologics and small molecules on epithelial repair, inflammation, and drug sensitivity.
• Explore rare epithelial lineages and their roles in homeostasis, inflammation, and regeneration.

In collaboration with Professor Roisin Owens (Department of Chemical Engineering and Biotechnology, University of Cambridge), we are now developing next-generation organoid platforms. These include:

• Bioelectronic interfaces for real-time physiological monitoring
• Advanced co-culture systems integrating epithelial, immune, and mesenchymal components
• Customised microenvironments and biomaterials that replicate the physical and chemical landscape of the gut

These innovations represent a critical advance in organoid complexity, fidelity, and scalability — directly aligned with our goals to personalise therapy and improve outcomes in children with IBD and related disorders.

IEOs are not merely a model system. They are a translational platform — offering a bridge from bench to bedside, and ultimately, to better care for young patients.